UNC93B1 chaperone fine-tunes TLR7 and TLR9 trafficking to maintain SLE tolerance
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A 50-minute expert lecture on the ImmuneZoom YouTube channel, published 15 October 2026, explains how UNC93B1, a 12-transmembrane chaperone for endosomal Toll-like receptors, differentially regulates TLR trafficking and function. Activated TLR7-RNA complexes are routed to multivesicular bodies to restrain self-RNA sensing, while TLR9 activation depends on a palmitoylation-depalmitoylation checkpoint. Missense UNC93B1 mutations such as D93I and R336 drive TLR7 hyperactivation and lupus-like disease in mice, matching early-onset SLE in humans. Blocking the checkpoint with DHHC or PPT1 knockdown, or with HDSS or TPS1 inhibitors, cuts type I interferon and cytokines in spontaneous SLE mice and in patient PBMCs, pointing to a possible therapeutic route.
Written by a model from the reports · updated 2 hours ago
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- youtube.comUNC93B1 chaperone fine-tunes TLR7 and TLR9 trafficking and SLE tolerance
A 50-minute expert lecture on the ImmuneZoom YouTube channel explains how UNC93B1, a 12-transmembrane chaperone for endosomal TLRs, differentially regulates TLR trafficking and function. Activated TLR7-RNA complexes are routed to multivesicular bodies to restrain self-RNA sensing, while TLR9 activation depends on a palmitoylation-depalmitoylation checkpoint. Mis-sense UNC93B1 mutations such as D93I and R336 drive TLR7 hyperactivation and lupus-like disease in mice, matching early-onset SLE in humans, and blocking the checkpoint with DHHC or PPT1 knockdown, HDSS or TPS1 inhibitors cuts type I interferon and cytokines in spontaneous SLE mice and patient PBMCs.
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